Articular cartilage provides a nearly frictionless surface joint movement and transmits loads from the cartilage surface to the subchondral bone. The ability to perform both functions depends on the integrity of the superficial layer of articular cartilage and its ability to resist wear. We have isolated a protein called the superficial zone protein (SZP) whose distribution in cartilage is restricted to the upper-most layer of the tissue. (SZP) is a mucinous glycoprotein, which displays a highly restricted distribution in articular cartilage. It is synthesized by the chondrocytes at the surface of the tissue and it accumulates in the cell-free matrix of the lamina splendens at the articular cartilage surface. In this region the molecule lubricates the cartilage surface and prevents cells from binding there. Although more is known about the SZP structure and possible functions, nothing is known about the transcription factors that control the highly regulated, regionspecific expression of this molecule. The experiments proposed in this application will begin to identify and characterize some of the transcription factors and DNA elements in the SZP gene that control its expression. SZP4uciferase reporter constructs containing DNA segments from the SZP promoter/enhancer regions Will be used to transfect chondrocytes and define regions important for the control of its transcription. EMSAa will be used to identify specific nucleotide sequences in SZP that bind transcription factors, which regulate SZP expression. An analysis of the effects of catabolic and anabolic cytokines and growth factors on SZP expression will help identify the DNA elements and transcription factor which enhance or suppress its expression. The influence of synovial fluid and biomechanical forces on SZP expression also will be investigated. These experiments will form the foundation for understanding how this interesting and potentially important macromolecule is regulated. This information may be directly applicable for the therapeutic use of increasing the joint lubrication in osteoarthritic patients or in the engineering of biological cartilage replacement tissues for OA patients with end-stage disease whose cartilage has been destroyed.